The preparation of carbamates of N-hydroxythioimidates by three generally applicable methods is known in the art: U.S. Pat. No. 3,576,834 and British Pat. No. 1,090,986:
(1) Reaction of the N-hydroxythioimidate with an isocyanate and a basic catalyst in an inert, anhydrous organic solvent, at elevated temperatures. ##STR1##
(2) Preparation of the N-hydroxythioimidate salt in aqueous solution, reaction of this aqueous solution with phosgene in a water immiscible organic solvent at 0.degree.-5.degree. C, separation of the organic layer containing the chloroformate ester, and reaction of this organic layer with an aqueous solution of an amine at 0.degree.-5.degree. C. ##STR2##
(3) Preparation of the salt of the N-hydroxythioimidate in an inert anhydrous organic solvent using sodium hydride or sodium amide as base; reacting this salt with a carbamoyl chloride. ##STR3##
Methods (1) and (3) require expensive reagents (CH.sub.3 NCO, NaH) and anhydrous conditions. Although a partially aqueous reaction medium is permitted in method (2), the reaction must be conducted at low temperature and involves the handling of poisonous phosgene.
Also, if a chemist skilled in the art adapted the reaction of an N-hydroxythioimidate with a carbamoyl chloride to an aqueous or partially aqueous system, he would expect the following side reactions to take place: ##STR4##
Further, it is known in the art that carbamoyl chlorides are destroyed by bases, particularly aqueous alkali. British Pat. No. 1,208,862 teaches that carbamoyl chlorides dissolved in a water-immiscible organic solvent and contacted with an aqueous base are transformed into isocyanates; U.S. Pat. No. 3,852,317 discusses the British Patent and discloses that isocyanates are extremely unstable in the presence of aqueous alkali, and that they are converted to a great extent into carbamates and carbamic acid. Therefore, it would be expected that basic pH would destroy methyl carbamoyl chloride (or methyl isocyanate) under the reaction conditions of this application and thus reduce the yield of the desired carbamate.
That such decomposition of methyl carbamoyl chloride by aqueous alkali is to be expected is demonstrated by the two experiments described below. In these experiments, methyl carbamoyl chloride in the water-immiscible solvent, methylene chloride, is contacted with aqueous base for a few minutes before S-methyl N-hydroxy-thioacetimidate is added. In Experiment (A), the pH of the aqueous phase is 10.1, and no reaction product is formed, showing that the methyl carbamoyl chloride was destroyed. In Experiment (B), the pH of the aqueous phase was 8.15 to 7.3, and a 52.6% yield of reaction product is obtained, showing that in the presence of a minor amount of base, about half of the methyl carbamoyl chloride is destroyed. Surprisingly, as demonstrated by the Examples of this patent application, we have discovered that the reaction can be carried out in the presence of base at pH 10 and above, without serious decomposition of methyl carbamoyl chloride, if S-methyl N-hydroxythioacetimidate is present while the base and methyl carbamoyl chloride are mixed.
(A) To 233.7 parts of a 22.0% solution of methyl carbamoyl chloride (0.55 mole) in methylene chloride was added within 5 minutes at 20.degree.-25.degree. C with cooling, 112 parts of 19.6% aqueous sodium hydroxide solution (0.55 mole). The pH was then adjusted to 10.1 with 50% sodium hydroxide solution and 52.5 parts of methylthiolacethydroxamate added. Stirring was continued at 20.degree.-25.degree. C for 15 minutes after which time the pH was still at 10.1. The pH of the reaction mass was then adjusted to 7.0 with conc. HC1, the lower, organic layer separated, dried and the solvent removed by evaporation under vacuum to give 54.3 parts of solids, m.p. 83.degree.-87.degree. C, which were identified by infrared analysis as slightly impure methylthioacethydroxamate.
(B) To 233.7 parts of a 22.0% solution of methyl carbamoyl chloride (0.55 mole) in methylene chloride was added within 5 minutes at 20.degree.-25.degree. with cooling, 112 parts of 19.6% aqueous sodium hydroxide solution (0.55 mole). After stirring an additional 5 minutes the pH stabilized at 8.15. Then 52.5 parts of methylthiolacethydroxamate was added and stirring continued for 15 minutes at 20.degree.-25.degree. C, after which time the pH decreased to 7.3. The lower, organic layer was then separated, dried, and the solvent removed by evaporation under vacuum to give 73.6 parts of waxy solids which assayed 57.9% methyl O-(methylcarbamoyl)thiolacethydroxamate by liquid chromatography. This represents a 52.6% yield from methylthiolacethydroxamate.